Phase IIb, Randomised, Double-blind, Placebo-controlled, Multi-centre Trial of Infliximab With Transcriptomic Biomarker and Mechanism Evaluation in Patients With Acute Pancreatitis.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 240
- 试验地点
- 27
- 主要终点
- Difference in mean serum CRP measured on days 2, 4 and 14
研究概览
简要总结
This study evaluates the effectiveness and safety of infliximab in the treatment of acute pancreatitis in adults. A third of participants will receive one single dose of infliximab via infusion, another third will receive a higher dose of infliximab via infusion and the final third of participants will receive a placebo infusion.
详细描述
Acute pancreatitis (AP) is an inflammatory disorder of the pancreas causing excruciating pain, gastrointestinal dysfunction and pronounced systemic inflammatory responses with circulatory and respiratory disturbances that can lead to organ failure and death.
Tumour necrosis factor alpha (TNFα) has a major role in the pathogenesis and severity of acute pancreatitis. TNFα levels rise early and remain elevated for days in human AP, proportional to severity, presenting a suitable drug target to inhibit the amplified immune responses that further damage the pancreas and drive widespread organ dysfunction.
Infliximab is a chimeric monoclonal antibody biologic drug that blocks the actions of tumor necrosis factor alpha (TNF-α) and is normally used to treat autoimmune diseases. Infliximab has been selected as it is given via intravenous infusion, which will ensure rapid bioavailability to treat AP. This is different from most other biologics, which are given subcutaneously.
This trial will determine the efficacy of early initiation of anti-TNF treatment in AP, setting new standards for trials in AP. Using a randomised, double-blind, placebo-controlled adaptive design, with two doses of a single intravenous infusion of infliximab at 5 mg/kg or 10 mg/kg (the higher dose arm was dropped on 19th May 2026, see Study Design), the trial will determine size of any effect and safety of this treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Once the delegated research team member performs randomisation and the staff member responsible for preparation of trial medication is provided with the allocation, that latter staff member will prepare the infusion, which will be covered by an opaque sleeve and labelled for blinding.
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients attending Accident and Emergency (A&E) at or admitted to recruiting hospitals via a GP with a new diagnosis of AP established by two of the following three criteria: (1) typical continuous upper abdominal pain; (2) amylase and/or lipase three or more times the upper limit of normal; (3) characteristic findings on abdominal imaging (if undertaken urgently by CT or MRI)
- •Patients in whom trial treatment can be started within 36 hours of admission to hospital with a new diagnosis of acute pancreatitis allowing 120 min for preparation of trial medication
- •Patients from whom appropriate consent is obtained (from the patient or their legal representative).
排除标准
- •Age <18 or >85
- •Patients with a bodyweight over 200 kg
- •Known previous AP within the last 30 days or chronic pancreatitis
- •Multiple sclerosis, systemic vasculitis, Guillain-Barré syndrome or other demyelinating disorder
- •Known epilepsy
- •Moderate to severe heart failure and/or coronary disease (NYHA III/IV)
- •Severe respiratory conditions including cystic fibrosis, severe asthma and severe chronic obstructive pulmonary disease (COPD)
- •On home oxygen or home mechanical ventilation
- •Jaundice (serum bilirubin >50 µmol/L), and/or known advanced liver disease, on waiting list for liver transplantation or considered unsuitable for transplantation
- •Known cancer for which chemotherapy and/or radiotherapy ongoing/completed in last 6 months
- •Known haematological malignancy
- •Known end-stage cancer requiring palliative care
- •Known established infection prior to or suspected infection, including COVID-19, at the time of AP onset
- •Known history of tuberculosis, or household contact with those with tuberculosis or opportunistic infection
- •Known history of infective hepatitis
- •Rare diseases or inborn errors of metabolism that significantly increase the risk of infections, including severe combined immunodeficiency (SCID) and homozygous sickle cell disease
- •Known live vaccine or infectious agent within one month of admission
- •Known immunosuppressive or biologic therapy within one month of admission
- •Known hypersensitivity to infliximab or to inactive components of REMICADE® or to any murine proteins
- •Known pregnancy or lactation at admission
- •Females of childbearing potential who do not agree to use adequate contraception up to 6 months after infliximab infusion
- •Known participation in investigational medicinal product study within last three months.
研究组 & 干预措施
Infusion of 5 mg/kg Infliximab
Infliximab (Remicade) to be administered as a one time intravenous infusion in 250 ml (500 ml if patient weighs over 100 kg) 0.9% sodium chloride solution over a period of 2 hours. Dosage calculated at 5 mg of Infliximab, per kg of patient body weight.
干预措施: Infusion of 5 mg/kg Infliximab (Drug)
Infusion of 10 mg/kg Infliximab
Infliximab (Remicade) to be administered as a one time intravenous infusion in 250 ml (500 ml if patient weighs over 100 kg) 0.9% sodium chloride solution over a period of 2 hours. Dosage calculated at 10 mg of Infliximab, per kg of patient body weight.
干预措施: Infusion of 10 mg/kg Infliximab (Drug)
0.9% Sodium Chloride (Placebo)
250 ml (500 ml if patient weighs over 100 kg) 0.9% Sodium Chloride to be administered as a one time intravenous infusion over a period of 2 hours.
干预措施: 0.9% Sodium Chloride (Placebo) (Other)
结局指标
主要结局
Difference in mean serum CRP measured on days 2, 4 and 14
时间窗: Days 2, 4 (+/- 1 day), and 14 (+/- 2 days)
Difference in mean serum CRP measured on (summated as AUC) in the active arms (5 mg/kg or 10 mg/kg) versus the placebo arm. CRP assays will be undertaken on blood samples centrally to ensure standardised measurement, and when central measurements of CRP at specific time points are not available for any patient, CRP measures from that patient's specific recruiting centre will be sought.
次要结局
- Decline in serum albumen(First 14 days)
- Mortality(Within the first 90 days)
- Anti-infliximab antibody concentration(Day 14)
- Incremental cost per quality adjusted life years (QALY) gained by trial treatment(Days 4, 14 and 90)
- Infliximab concentration(Day 14)
- Opiate requirements(First 14 days)
- Rise in neutrophils(First 14 days)
- Sequential organ failure assessment (SOFA) score(First 14 days)
- Local pancreatic injury(Day 14 +/- 7 days)
- Pain scores(First 14 Days)
- Nutritional deficit(First 14 days)
- Length of hospital stay(Up to 90 days)
- Revised Atlanta Classification (RAC)(90 days after admission)
- Infective complications(First 90 days)
- Patient reported outcome(Day 4, Day 14 and Day 90)
- Potential safety signals(Up to 90 days)